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• W4385684212 abstract "ABSTRACTBackground The potential mechanism underlying the association between Homologous recombination deficiency (HRD) and immunotherapy in colon cancer has not been investigated.Methods The exon sequencing data and transcriptome data of 456 colon adenocarcinoma (COAD) patients were obtained from the TCGA database. Pathway activity score was calculated by GSVA methods and engaged in further survival analysis. The prognostic value of the candidate pathways was validated in an external GEO cohort and an immunotherapy cohort.Results Patients with high HRD were associated with poor prognosis, lower tumor mutation burden and microsatellite instability, higher fraction genome alteration, and less sensitivity to immunotherapy in COAD. And then, the neuroactive ligand–receptor interaction pathway was over-activated in high-HRD tumors and associated with immunosuppression in colon cancer with high HRD. Besides, the pathway was associated with prognosis and immunotherapy response in COAD. Moreover, genes in this pathway such as LTB4R2 can be used as a novel target for therapy development in colon cancer.Conclusion Our study not only revealed the potential mechanism of HRD and the function of the neuroactive ligand–receptor interaction pathway in colon cancer but also provided new clues for the improvement of immunotherapy response in colon cancer.KEYWORDS: Homologous recombination deficiencycolon adenocarcinomathe neuroactive ligand–receptor interaction pathwayimmunoregulationimmunotherapy response AcknowledgementsWe thank the support of Beijing Friendship Hospital and Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases in this study.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Author contribution statementConceptualization, Yun Yang, Jun Li, Chao Jing, Yuhao Zhai, Zhigang Bai, Yingchi Yang and Wei Deng; Methodology, Yun Yang, Jun Li, Chao Jing; Software, Yun Yang; Validation, Yun Yang, Yuhao Zhai, and Zhigang Bai; Formal Analysis, Yun Yang, Yingchi Yang, and Wei Deng; Investigation, Yun Yang, Yingchi Yang, and Wei Deng; Resources, Yun Yang; Data Curation, Yun Yang, Yingchi Yang, and Wei Deng; Writing – Original Draft Preparation, Yun Yang; Writing – Review & Editing, Yun Yang, Jun Li, Chao Jing, Yuhao Zhai, Zhigang Bai, Yingchi Yang and Wei Deng; Visualization, Yun Yang, Jun Li, Chao Jing, Yuhao Zhai, and Zhigang Bai; Supervision, Yingchi Yang and Wei Deng; Project Administration, Yun Yang, Yingchi Yang and Wei Deng; Funding Acquisition, Yun Yang.Data availability statementThe datasets generated and/or analyzed in this study were obtained from the public database: the TCGA database (https://portal.gdc.cancer.gov); the cBioPortal database (http://www.cbioportal.org/study/summary?id=coadread_tcga_pan_can_atlas_2018; https://www.cbioportal.org/study/summary?id=skcm_dfci_2015), and the GEO database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse41258).Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2023.2245567Additional informationFundingThis paper received no funding." @default.
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• W4385684212 date "2023-08-24" @default.
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• W4385684212 title "Inhibition of neuroactive ligand–receptor interaction pathway can enhance immunotherapy response in colon cancer: an in silico study" @default.
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• W4385684212 doi "https://doi.org/10.1080/14737140.2023.2245567" @default.
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